Pulmonic stenosis in infants and children: Management and outcome

INTRODUCTION — Right ventricular outflow tract (RVOT) obstructive lesions are characterized by obstruction to flow from the RV to the pulmonary arteries (PAs). Obstruction can occur at different levels, including valvular pulmonic stenosis (PS), subvalvular PS, supravalvular PS, and peripheral PS (PPS). These lesions can occur in isolation or may be associated with other cardiac defects (eg, tetralogy of Fallot, tricuspid atresia).

The management and outcome of isolated valvular, subvalvular, and supravalvular PS and PPS in infants and children will be reviewed here. The pathophysiology, clinical features, and diagnosis of PS in infants and children and other RVOT obstructive lesions (eg, tetralogy of Fallot and tricuspid atresia) are discussed separately:

●(See "Pulmonic stenosis in infants and children: Clinical manifestations and diagnosis".)

●(See "Tetralogy of Fallot (TOF): Pathophysiology, clinical features, and diagnosis" and "Tetralogy of Fallot (TOF): Management and outcome".)

●(See "Tricuspid valve atresia".)

PS in adults is also discussed separately:

●(See "Clinical manifestations and diagnosis of pulmonic stenosis in adults".)

●(See "Pulmonic valve stenosis in adults: Management".)

●(See "Echocardiographic evaluation of the pulmonic valve and pulmonary artery".)

SEVERITY — The clinical manifestations, natural course, and management of PS vary depending on the severity of obstruction, which is determined by estimating the pressure gradient across the pulmonary valve using echocardiography (table 1):

●Mild – Maximum instantaneous gradient (MIG) by Doppler echocardiography <40 mmHg

●Moderate – MIG 40 to 60 mmHg

●Severe – MIG >60 mmHg

The pressure gradient can also be directly measured by cardiac catheterization; however, cardiac catheterization is primarily used for therapeutic intervention and is rarely performed solely for diagnostic purposes in children with PS. There is generally good correlation between the Doppler-derived gradient and that obtained by direct catheterization measurements. However, because cardiac catheterization is typically performed with the patient sedated, catheter measurements are typically lower than corresponding echocardiographic estimates (eg, a catheterization measurement of 40 mmHg in a sedated patient corresponds roughly to a Doppler-derived gradient of 60 mmHg in an awake patient). The gradient measured in the catheterization laboratory is considered the gold standard.

NATURAL HISTORY — The natural course of patients with valvular PS varies with the severity of the defect and age at initial presentation.

●Mild valvular PS (gradient <40 mmHg) – Mild valvular PS is generally benign and, in patients older than one or two years, PS is unlikely to progress to more serious disease [1,2].

A retrospective single-center study of 146 patients with mild valvular PS diagnosed by echocardiography (median age at diagnosis 3.9 months) reported progression of disease in only two patients after a mean follow-up of four years [1]. Both patients with progressive disease were diagnosed as young infants [1]. Of the remaining patients at follow-up, 103 had very mild disease, with a pressure gradient ≤25 mmHg, and 16 had a pressure gradient between 25 mmHg and <40 mmHg.

In another study of 147 patients, progression from mild to moderate or severe PS occurred in 11 of 40 neonates and in 10 of 68 patients over one month of age [2]. In contrast, no patient initially evaluated over the age of two years who had a gradient <50 mmHg progressed to severe obstruction.

Additional evidence supporting a benign course for mild PS includes an older natural history study (the First Natural History Study of Congenital Heart Defects [NHS-1]) of 565 children with PS who underwent initial cardiac catheterization between 1958 and 1969 [3]. In NHS-1, only 3 of 261 patients with mild stenosis (pressure gradient <25 mmHg on catheterization) who were treated medically developed severe PS (pressure gradient >60 mmHg) over a four- to eight-year period. A subsequent long-term follow-up study of this cohort (the Second Natural History Study of Congenital Heart Defects [NHS-2]) showed that only 4 percent of children with mild PS who were managed medically subsequently underwent valvotomy [4].

●Moderate valvular PS (gradient 40 to 60 mmHg) – The natural course of moderate valvular PS varies. Data from NHS-1, NHS-2, and another similar natural history study suggest that some patients with moderate PS may develop more progressive right ventricular outflow tract (RVOT) obstruction over time [3-5]. In NHS-2, approximately 20 percent of patients with moderate PS ultimately required surgical correction, presumably because of progressive symptoms or RV dysfunction [4]. Children with moderate PS survive into adulthood with life expectancies that are not different from the general population; however, some patients may develop exercise intolerance and fatigue after the second decade of life due to limitation of RV cardiac output. (See "Pulmonic valve stenosis in adults: Management", section on 'Moderate stenosis'.)

●Severe valvular PS (gradient >60 mmHg) – Severe valvular disease does not appear to remit and may progress during childhood [3]. These patients already have evidence of increased RV end-diastolic pressure and, in some patients, RV hypertrophy, which if untreated, results in irreversible RV dysfunction [6-8].

●Peripheral PS (PPS) – PPS in the setting of a normal electrocardiogram and in the absence of syndromic disease is generally mild, does not progress, and often regresses [9,10]. In patients with Alagille or Williams-Beuren syndrome, PPS is typically more severe and usually requires intervention.

●Supravalvular PS – Congenital supravalvular PS is extremely rare and can be mistaken for valvular PS due to its close proximity to the pulmonary valve. Iatrogenic supravalvular PS can occur after procedures involving the main pulmonary artery (PA), such as arterial switch operation (as high as 20 percent of these patients in one report), repair of tetralogy of Fallot, and PA band placement [11]. Supravalvular PS can occur in patients with Williams-Beuren syndrome, though isolated supravalvular PS without distal stenosis is uncommon.

●Subvalvular PS – Subvalvular PS is usually associated with tetralogy of Fallot. Isolated congenital subvalvular stenosis is rare. (See "Tetralogy of Fallot (TOF): Pathophysiology, clinical features, and diagnosis".)

MANAGEMENT

General considerations — Important considerations in the management of PS include:

●Neonates with critical PS require urgent intervention. (See 'Critical pulmonic stenosis' below.)

●In stable patients, the choice between intervention or conservative management is largely based on the severity of PS. (See 'Management approach' below.)

●When intervention is indicated, balloon pulmonary valvuloplasty (BPV) is generally the procedure of choice. However, surgical correction may be required in some cases (eg, supravalvular and subvalvular PS as well as some patients with dysplastic pulmonary valves and a hypoplastic annulus or main pulmonary artery [PA]). (See 'Transcatheter procedures' below and 'Surgery' below.)

Management approach — Based on the natural course of PS, the indications for catheter-based or surgical intervention are determined largely by the severity of the pressure gradient across the right ventricular outflow tract (RVOT), which is typically determined by echocardiography and, in some cases, cardiac catheterization. Our recommendations are generally consistent with the recommendations of the American Heart Association (AHA), with the distinction that the AHA's indications for BPV are based on the resting gradient as determined with the patient sedated in the catheterization laboratory [12]. Our recommendations are based on the maximum instantaneous gradient (MIG) as estimated by Doppler echocardiography, which is typically performed without sedation. Thus, for the gradients provided below, corresponding catheterization-based measurements are generally lower.

Critical pulmonic stenosis — Critical PS is a life-threatening condition in the neonate because of inadequate antegrade pulmonary flow through the RVOT. Survival is dependent on maintaining patency of the ductus arteriosus by the administration of prostaglandin E1 (alprostadil) therapy, thereby providing adequate pulmonary blood flow [13]. (See "Diagnosis and initial management of cyanotic heart disease in the newborn", section on 'Prostaglandin E1'.)

Once the neonate is medically stable, definitive intervention should be performed. BPV is the procedure of choice since it is as effective as surgical correction and is less invasive [14]. However, urgent surgical intervention may be required if BPV fails. Prostaglandin therapy can be discontinued following dilation; however, infants may remain cyanotic over weeks with residual right-to-left shunting through a patent foramen ovale because of persistent RV noncompliance. This typically resolves over time, but, in some cases, additional pulmonary blood flow with a surgically placed aortic-to-pulmonary artery shunt (modified Blalock-Thomas-Taussig shunt (figure 1) or central shunt) may be required.

Severe pulmonic stenosis (gradient >60 mmHg) — For patients with severe PS (defined as maximum gradient >60 mmHg by Doppler echocardiography, which roughly corresponds to a gradient of >40 mmHg when measured under sedation by cardiac catheterization), we recommended catheter-based or surgical intervention. The goal of intervention is to improve symptoms and prevent irreversible cardiac injury. BPV is the preferred procedure in patients with typical valvular dome-shaped PS. Surgery is generally reserved for patients with dysplastic pulmonary valves and hypoplastic annulus or main PA, or for those with supravalvular or subvalvular PS. (See 'Balloon pulmonary valvuloplasty' below and 'Surgery' below.)

Patients with severe PS are typically symptomatic and present with cyanosis as well as dyspnea and fatigue with exertion. Irreversible RV dysfunction can develop if not corrected. (See 'Natural history' above.)

Moderate pulmonic stenosis (gradient 40 to 60 mmHg) — Patients with moderate PS are at risk for developing more severe PS or becoming symptomatic later in life due to RV dysfunction. We monitor these patients on an annual basis. (See 'Follow-up care' below.)

Practice varies regarding the criteria for intervention in children with moderate PS. Because of the excellent success rate and minimal risk of BPV, and because of the long-term consequences of unrepaired lesions, we suggest BPV for patients who continue to have gradients approaching 60 mmHg. Some centers may use a slightly lower gradient (around 50 mmHg) as a threshold for catheter-based intervention in older children and adolescents. BPV is also indicated for patients who develop symptoms (eg, school-aged children who become exercise-intolerant). (See 'Balloon pulmonary valvuloplasty' below.)

Mild pulmonic stenosis (gradient <40 mmHg) — Mild valvular PS is generally benign, and these patients do not require intervention. Although most mild PS will not progress, we continue to monitor patients with echocardiography. (See 'Follow-up care' below.)

Peripheral pulmonic stenosis — Intervention for peripheral PS (PPS) is generally warranted if there is marked decrease in flow to the affected lung segment demonstrated by radionuclide scan, elevated RV pressure that is greater than one-half the systemic pressure, and/or clinical symptoms of fatigue or decrease in exercise tolerance [15-17]. Intervention typically consists of balloon angioplasty. (See 'Balloon angioplasty' below.)

Transcatheter procedures

Balloon pulmonary valvuloplasty — BPV is a transcatheter procedure that is usually performed via femoral venous access. A catheter and wire are introduced and advanced across the pulmonary valve. A balloon 120 to 140 percent the size of the pulmonary valve annulus is used to dilate the pulmonary valve (image 1).

●Valvular pulmonic stenosis – BPV is the first line treatment for the typical dome-shaped valvular PS since it is an effective intervention with rare complications [18-23]. Among patients with this type of PS treated with BPV, more than 90 percent achieve a gradient <20 mmHg (image 2) [24,25].

BPV may be successful in select patients with valvular PS associated with dysplastic pulmonary valves; however, surgical correction is generally needed for patients with either a hypoplastic annulus or main PA and for those who fail BPV. (See 'Surgery' below.)

As discussed above, BPV is the preferred treatment in neonates with critical PS (image 1 and movie 1 and image 3) [26,27]. (See 'Critical pulmonic stenosis' above.)

●Other pulmonic stenosis variants – BPV is not an effective intervention in cases of supravalvular PS, due to the close proximity of the stenotic area of the PA to the pulmonary valve. Similarly, BPV is not effective in patients with subvalvular PS. In these cases, surgical repair is necessary. (See 'Surgery' below.)

Balloon angioplasty — Balloon angioplasty is commonly used to treat PPS [15-17,28-32]. A balloon two to four times the diameter of the narrowed segment is required to dilate the PPS. Vessels resistant to pulmonary angioplasty can be addressed with high-pressure balloons, cutting balloons, or stents.

Complications

●Procedural complications – Overall, procedural complications for BPV and balloon angioplasty for PS and PPS are extremely rare. They can include [14,22]:

•Perforation of the pulmonary valve or RV with oversized balloon use

•Tricuspid valve injury resulting in regurgitation

•Femoral vein occlusion, which is seen most commonly in small infants

●Pulmonary regurgitation (PR) – Following BPV, most patients develop some degree of PR [23]. Careful selection of balloon size should reduce the degree of PR [14]. However, balloon dilations performed in the early era of BPV often resulted in moderate to severe PR and RV dilation [26,33].

There is no consensus regarding timing for pulmonary valve replacement (PVR) in the setting of severe PR after valvular PS intervention. For patients who require PVR, options include transcatheter or surgical PVR. Data are lacking in this patient population, and considerations regarding need for PVR, timing, and choice of procedure in this setting are often extrapolated from the experience in patients with tetralogy of Fallot, which is discussed separately. (See "Tetralogy of Fallot (TOF): Management and outcome" and "Tetralogy of Fallot (TOF): Long-term complications and follow-up after repair", section on 'Pulmonary valve replacement (PVR)'.)

Surgery — Surgical valvotomy may be performed as an open procedure requiring cardiopulmonary bypass or through a closed transventricular approach. Access is through a median sternotomy for both operations.

Surgery is not usually needed to treat typical valvular PS. However, surgery is often needed in patients with dysplastic pulmonary valves and a hypoplastic annulus or main PA [22,34]. In these patients, surgical repair is required to excise thickened and obstructive valve leaflets and place a transannular patch.

Surgery is also the intervention of choice for patients with subvalvular PS, because the muscular nature of this lesion is not amenable to balloon dilation, and requires muscular resection and often infundibular patch. It is also the preferred procedure in patients with supravalvular PS, because the stenotic area of the PA is in close proximity of the pulmonary valve, and requires patch placement.

Surgery is also used to correct moderate and severe PPS in patients with Williams-Beuren and Alagille syndromes [35].

LONG-TERM OUTCOME — As previously discussed, the long-term prognosis of uncorrected PS depends on the severity of the obstruction. (See 'Natural history' above.)

Outcomes following percutaneous balloon pulmonary valvuloplasty (BPV) and surgical correction of PS are excellent:

●Outcome following BPV – Long-term data on BPV were presented in a single tertiary center study of 150 pediatric patients with a mean follow-up of 12 years [23]. Freedom from reintervention was 90, 83, and 77 percent at 1, 10, and 15 years follow-up, respectively. In another pediatric series of 85 patients, restenosis (defined as a gradient >50 mmHg) was observed in nine patients over the 3- to 10-year follow-up period and the freedom from reintervention was 94, 88, and 84 percent at 1, 5, and 10 years, respectively [25].

●Outcome following surgery – The long-term results of patients treated with surgical valvotomy are excellent, with reported survival rates of 93 percent at a mean follow-up period of 25 years [36]. In the Second Natural History Study (NHS-2), 96 percent of surgically treated patients remained free of reoperation at 10 years after the initial intervention [4]. In a separate study of 53 patients (mean age at time of surgery was 10 years) with an average follow-up of 33 years, approximately one-half of the cohort required reoperation, primarily pulmonary valve replacement for severe pulmonary regurgitation (PR) [37]. There have been advances in surgical technique since the early era during which patients in these studies were initially treated (ie, the 1950s through the 1970s). Thus, it is likely that the incidence of severe PR is considerably lower in patients operated on in the modern era.

There are few available data on outcomes of children with supravalvular PS. One center reported that among infants and children who underwent repair of native supravalvular PS, no patients required reintervention at two years out [11]. In another single-center report of children with iatrogenic supravalvular PS after arterial switch operation, freedom from reoperation was 80 percent at 15 years and 66 percent at 20 years post-repair [38].

There are no published data regarding isolated subvalvular PS. Outcomes in children with subvalvular PS in the setting of tetralogy of Fallot are discussed separately. (See "Tetralogy of Fallot (TOF): Management and outcome", section on 'Long-term outcomes'.)

HEALTH CARE MAINTENANCE

Follow-up care — The need and timing for long-term cardiac follow-up varies with the degree of obstruction and whether the patient has undergone intervention.

At each visit, a focused cardiac history that includes exercise tolerance, physical examination, and testing that includes electrocardiography and echocardiography are performed. In our center, we use the following approach:

●Mild stenosis (gradient <40 mmHg) – Patients with mild stenosis are initially followed at six-month intervals until they reach one or two years of age. If the gradient regresses to <25 mmHg, follow-up can be done at five-year intervals. If the gradient remains between 25 and 40 mmHg after one year, the frequency of follow-up can be decreased, with follow-up at one year following the second echocardiography and then subsequent follow-up every three years. Of note, women with mild PS can develop more severe disease during pregnancy. Hence, it is important to continue to monitor these patients through adulthood. (See "Pregnancy and valve disease".)

●Moderate stenosis (gradient 40 to 60 mmHg) – Patients with moderate PS are monitored every one to two years. If the pressure remains consistently >55 mmHg or symptoms develop, refer the patient for catheter-based or surgical intervention (in most cases of valvular PS, balloon pulmonary valvuloplasty [BPV] is the preferred procedure, as previously discussed). (See 'Management' above.)

●After intervention – If the gradient remains mild after intervention, follow-up visits are conducted every year initially for the first two years and subsequent visits are performed every three to five years; the frequency depends on the individual patient's clinical status. Patients are monitored for evidence of restenosis and for evidence of clinically significant pulmonary regurgitation (PR):

•Restenosis – Reintervention is considered if there is evidence of restenosis, using the same criteria used for initial dilation. Other factors used to consider reintervention include increased right ventricular outflow tract (RVOT) obstruction, RV hypertrophy, or RV dysfunction.

•PR – Cardiac magnetic resonance imaging is useful to determine the degree of PR and RV size and function. For patients who require pulmonary valve replacement (PVR) due to PR, options include transcatheter or surgical PVR. Data are lacking in this patient population, and considerations regarding need for PVR, timing, and choice of procedure are often extrapolated from the experience in patients with tetralogy of Fallot, which is discussed separately. (See "Tetralogy of Fallot (TOF): Management and outcome" and "Tetralogy of Fallot (TOF): Long-term complications and follow-up after repair", section on 'Pulmonary valve replacement (PVR)'.)

Activity — Most patients with PS do not require any restriction on exercise or physical activity. The 2015 scientific statement of the American Heart Association and American College of Cardiology (AHA/ACC) provides competitive athletic participation guidelines for patients with congenital heart disease, including PS [39]:

●Patients with mild PS (gradient <40 mmHg) and normal RV function can participate in all competitive sports. Annual reevaluation is recommended.

●Patients treated with BPV or surgery who have achieved adequate relief of PS (gradient <40 mmHg) can participate in all competitive sports.

●Patients with moderate or severe PS (gradient >40 mmHg) and those with severe PR (as demonstrated by marked RV enlargement) may participate only in low-intensity class IA and IB sports (figure 2).

There is little evidence to support the AHA/ACC recommendations, and they are based largely on expert opinion [39]. We generally agree with the recommendations, with the exception that we do not restrict activity in most patients with moderate PS (gradient 40 to 60 mmHg).

Physical activity and exercise in patients with congenital heart disease are discussed in detail separately. (See "Physical activity and exercise in patients with congenital heart disease".)

Antibiotic prophylaxis — Patients with PS do not require antibiotic prophylaxis for the prevention of endocarditis. (See "Prevention of endocarditis: Antibiotic prophylaxis and other measures".)

SUMMARY AND RECOMMENDATIONS

●Severity of obstruction – The natural course and management of pulmonic stenosis (PS) in children vary depending on the severity of obstruction, which is determined by measuring the pressure gradient across the pulmonary valve (table 1). (See 'Severity' above and 'Natural history' above.)

●Valvular PS – The decision to perform a valve intervention in pediatric patients with valvular PS is based on the severity of PS while the choice of procedure is determined by the anatomy. For most patients with typical dome-shaped valvular PS who require intervention, we suggest transcatheter balloon pulmonary valvuloplasty (BPV) rather than surgical valvotomy (Grade 2C). This is because BPV is less invasive and appears to be equally effective. For patients with dysplastic pulmonary valves, BPV may be successful in select cases; however, surgical valvotomy is generally required for patients with a hypoplastic annulus or main pulmonary artery and for those who fail BPV. (See 'General considerations' above and 'Long-term outcome' above.)

The general management approach according to severity is as follows (see 'Management approach' above):

•Critical PS – Neonatal critical PS is a life-threatening condition and requires urgent intervention. Management includes prompt administration of prostaglandin E1 (alprostadil) to maintain patency of the ductus arteriosus, followed by definitive intervention with BPV once the neonate is medically stable. (See 'Critical pulmonic stenosis' above.)

•Severe PS (gradient >60 mmHg) – For infants and children with severe PS, we recommend intervention (typically with BPV) rather than conservative management (Grade 1B). Uncorrected severe PS results in irreversible right ventricular injury. (See 'Severe pulmonic stenosis (gradient >60 mmHg)' above.)

•Moderate PS (gradient 40 to 60 mmHg) – For patients with a gradient in the higher end of this range (ie, approaching 60 mmHg) and those who develop symptoms attributable to PS (eg, exercise intolerance), we suggest intervention (typically with BPV) rather than conservative management (Grade 2C). However, the criteria for intervention in this group are uncertain and other centers may use a different threshold. (See 'Moderate pulmonic stenosis (gradient 40 to 60 mmHg)' above.)

•Mild PS (gradient <40 mmHg) – Mild PS is a benign condition and generally does not require intervention. However, ongoing monitoring is needed, especially during the first two years of life, as more severe obstruction may develop in a small number of patients. (See 'Mild pulmonic stenosis (gradient <40 mmHg)' above and 'Follow-up care' above.)

●Other PS variants – Patients with severe subvalvular or supravalvular PS generally require surgical correction since BPV is not effective in these cases. Patients with severe obstruction due to peripheral PS (PPS) are commonly managed with balloon angioplasty (See 'Surgery' above and 'Balloon angioplasty' above.)

●Outcomes – The long-term outcome for children with PS who undergo transcatheter or surgical intervention is excellent. (See 'Long-term outcome' above.)

●Follow-up care – The level of cardiac follow-up is dependent on the degree of obstruction and whether the patient has undergone intervention. At each visit, a focused cardiac history, physical examination, and testing that includes electrocardiography and echocardiography are performed. (See 'Follow-up care' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Stanton Perry, MD, who contributed to an earlier version of this topic review.